Mouse models of experimental autoimmune uveitis

Abstract

The mouse model of experimental autoimmune uveitis, induced by immunization of mice with the retinal protein IRBP, was developed in our laboratory 20 years ago and published in 1988. Since that time it has been adopted by many investigators and has given rise to many studies that helped elucidate genetic influences, dissect the basic mechanisms of pathogenesis and test novel immunotherapeutic paradigms. The current overview will summarize the salient features of the experimental autoimmune uveitis model and discuss its mechanisms.

Fig. 1

EAU in HLA class II transgenic mice. Mice of the indicated strains were immunized with 200 µg of S-Ag in CFA and were given pertussis toxin as an additional adjuvant. Eyes were collected for 35 days after immunization. Shown are scores by histopathology graded on a scale of 0–4 according to the number and size of lesions, using published criteria [5].

Fig. 2

IL-17 vs. IFN-γ in CFA-EAU. a B10.RIII mice were immunized with IRBP. Lymph node cells draining the site of immunization were collected on day 21 and were stimulated in vitro with IRBP. Cytokines in 24-hour supernatants were assayed by multiplex ELISA (www.SearchLightOnline.com). b Eyes from uveitic mice were collected 16 days after immunization and were made into single-cell suspensions using mechanical and enzymatic dissociation of the tissues. The isolated cells were stained for CD4 and were analyzed by intracellular staining for IFN-γ and IL-17 using a published protocol. Shown are cells gated on CD4. c,d Mice were immunized for EAU and were treated with neutralizing antibodies to IL-17 (c) or IFN-γ (d). Eyes were collected approximately 1 week after disease onset in controls and were scored for EAU by histopathology.